Lysosomal-targeted near-infrared phototherapy agent with type-I photodynamic activity for high-performance synergistic therapy under hypoxia

The development of near-infrared (NIR) multifunctional phototherapy agents is important for expanding the application of photodynamic therapy (PDT)/photothermal therapy (PTT) for tumor diagnosis and treatment. Here, we constructed a phototherapeutic agent, CYPT nanoparticles (NPs), based on a cyanine dye (Cy7) for synergistic NIR image-guided tumor-specific PDT/PTT. CYPT NPs produced large amounts of type I O 2 •− and type II 1 O 2 under 808-nm laser irradiation with a high photothermal conversion efficiency (33.5%). Moreover, CYPT NPs targeted the lysosomes of cancer cells and reduced GSH, contributing to the high efficiency of PDT. CYPT NPs had similar inhibitory effects on 4T1 cells under hypoxic and normoxic conditions. Experiments in tumor-bearing mice confirmed that CYPT NPs can be enriched in tumor tissues, have good NIR fluorescence imaging performance, and exhibit efficient synergistic PDT/PTT, thus providing an attractive method for accurate tumor targeting and efficient treatment.